The effects of FK778 in combination with tacrolimus and steroids: a phase II multicenter study in renal transplant patients

Y. Vanrenterghem*, J.P. van Hooff, M. Klinger, Z. Wlodarczyk, J.P. Squifflet, G. Mourad, P. Neuhaus, A. Jurewicz, L. Rostaing, B. Charpentier, L. Paczek, H. Kreis, R. Chang, L.C. Paul, J.M. Grinyo, C. Short

*Corresponding author for this work

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The effects of FK778 in combination with tacrolimus and steroids: a phase II multicenter study in renal transplant patients.

Vanrenterghem Y, van Hooff JP, Klinger M, Wlodarczyk Z, Squifflet JP, Mourad G, Neuhaus P, Jurewicz A, Rostaing L, Charpentier B, Paczek L, Kreis H, Chang R, Paul LC, Grinyo JM, Short C.

Inwendige Geneeskunde-Nefrologie, Universitaire Ziekenhuizen Gasthuisberg, Leuven, Belgium.

BACKGROUND: In animal and in vitro models, FK778 inhibits acute rejection, modifies vasculopathy, and shows anti-viral activity. We report first efficacy and safety data of FK778 in human kidney transplant recipients at two concentration-controlled ranges. METHODS: In a double-blind manner, 149 patients were randomized to a 12-week treatment with FK778 in combination with tacrolimus (Tac) and corticosteroids (S). Of the high-level group (H), 49 patients received 2 x 600 mg/day FK778 and continued on 150 mg/day, 54 patients of the low-level group (L) got 1 x 600 mg/day followed by 75 mg/day, and 46 patients received placebo (P). Subsequent FK778 doses were adjusted to trough levels of 100-200 microg/mL (H) and 10-100 microg/mL (L). The primary endpoint was the incidence of biopsy proven acute rejection (AR). RESULTS: In 93% of the patients in group L, targeted plasma trough levels were reached by Day 3; in half of the patients in group H, the targeted levels were reached by Day 9. Graft survival at week 16 was 89.7%, 88.8%, and 91.3%, and the incidences of AR were 26.5%, 25.9%, and 39.1% for groups H, L, and P. For the subgroup of patients in which target levels were reached by week 2, incidences were 7.7%, 27.1%, and 39.1%, respectively. Anemia, the most frequently reported adverse event especially in group H, was reversible. Mean total cholesterol and LDL-cholesterol levels were reduced during FK778 treatment compared with group P. CONCLUSION: FK778 is pharmacologically active, well-tolerated, and safe. To fully benefit from this promising new drug, FK778 dosing will be optimized in subsequent studies
Original languageEnglish
Pages (from-to)9-14
Issue number1
Publication statusPublished - 1 Jan 2004

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